Challenging Diagnosis of Intrapancreatic Accessory Spleen in the Tail of the Pancreas: A Case Report

Background

The incidence of pancreatic ductal adenocarcinoma is increasing by 0.5% to 1.0% per year [1] and is expected to become the second leading cause of cancer-related death by 2030. Most patients with pancreatic cancer develop nonspecific symptoms at an advanced stage, and the disease is unsuitable for curative surgery. There is no effective screening. Although the 5-year survival rate of pancreatic cancer has almost doubled in the past decade, it is still only 10% (5.26% in 2000) [2]. In addition, the lack of effective biomarkers for pancreatic cancer, coupled with the inability of imaging diagnostics to distinguish pancreatic cancer from conscientious space-occupying pancreas lesions effectively, contributes to the prevalence of thousands of unnecessary medical and surgical interventions each year [3]. These high-risk procedures carry significant comorbidities, particularly in older adults [4]. Therefore, for patients with pancreatic space-occupying lesions, it is of great significance to use effective methods to classify the patients at risk and distinguish the nature of space-occupying lesions to reduce unnecessary surgical injuries caused by pancreatic surgery.

Intrapancreatic accessory spleen (IPAS) is a rare, benign pancreatic disease. On imaging, it is easy to misdiagnose IPAS as intrapancreatic space-occupying lesions, especially pancreatic neuroendocrine tumors [5–7]. The incidence of accessory spleen ranges from 20% to 30%. It was closely related to the main splenic hilum in 41% of cases and was involved with the tail of the pancreas in 11% of cases. The splenorenal ligament near the lower pole was found to be 23%, the gastrosplenic ligament at the upper pole was 13%, the greater omentum was 7%, and the left subphrenic connective tissue was 4% [7,8]. Histologically, IPAS is similar in structure to the normal spleen [9]. IPAS is an asymptomatic benign lesion detected incidentally on imaging studies and does not require surgery or follow-up. Nevertheless, based on the current reports, the diagnosis of IPAS mostly depends on histopathological examination after surgery [10]. This also means that almost all patients with IPAS have undergone excessive surgical treatment, resulting in substantial surgical trauma.

The most important differential diagnosis for IPAS is the asymptomatic pancreatic neuroendocrine tumors (PNETs). In the current literature, a significant proportion of pre-operative diagnoses of IPAS are non-functional PNETs [11,12]. IPAS and PNETs have similar and almost equal sex distributions, typically at age 60 years. Clinical symptoms or signs do not provide a powerful means of differential diagnosis. The main differences between the 2 are: (1) pancreatic neuroendocrine tumors account for 1% to 5% of all pancreatic tumors [13]; (2) IPAS mainly occur in the tail of the pancreas, while PNETs mainly occur in the head of the pancreas [14]; and (3) the volume of PNETs is usually larger [15]. Solid pseudopapillary neoplasm (SPN) is another entity that needs to be differentiated from IPAS. SPN accounts for approximately 1% to 3% of pancreatic tumors [16]. It occurs mainly in female patients aged 20 to 40 years and is located in the body or tail of the pancreas. It has a low potential for malignancy [17]. The most common imaging findings were extensive, well-encapsulated, heterogeneous masses with hemorrhagic, cystic, or calcified degeneration [18]. There are some difficulties in the differential diagnosis of SPN, PNETs, and IPAS. IPAS does not require treatment, whereas SPN is an aggressive tumor with a 5-year survival rate of up to 94% to 97% [19, 20], with most patients presenting with localized disease and less than 15% having metastasis or local invasion [21]. PNETs are more complex and have a worse prognosis than IPAS and SPNS. SPN and IPAS are more common in the tail of the pancreas, but SPN is more common in women. SPN shows hemorrhagic degeneration and heterogeneous enhancement and is more extensive than IPAS and PNETs [18]. This may shed some light on the differential diagnosis of the 3 tumors.

The imaging appearance of IPAS is a round, highly vascular, and well-circumscribed mass in the tail of the pancreas [22]. Heterogeneous enhancement of IPAS at an early stage can be an essential diagnostic clue [23]. In addition, superparamagnetic iron oxide can be used as a diagnostic tool for IPAS to improve the diagnostic efficiency of IPAS [24,25]. On endoscopic ultrasound (EUS), IPAS appears as a circular homogeneous echogenetic texture, similar to the adjacent spleen, with hypervascularization and possibly less echogenicity than the surrounding pancreas [26–28]. Previous studies have shown that EUS has difficulty distinguishing between benign and malignant tumors of the pancreas [29–31]. EUS-FNA is considered to be a reliable method for the diagnosis of IPAS. Cytologically, a mixture of hematopoietic cells (including lymphocytes, neutrophils, eosinophils, histiocytes, and plasma cells) with a background of vascular-like structures and CD8 immunostaining can highlight splenic endothelial cells as an influential feature of IPAS432-35]. This report presents a challenging case of IPAS in the tail of the pancreas in a 64-year-old man.

Case Report

A 64-year-old man with no notable medical history was admitted to the hospital principally because a “physical examination revealed a space-occupying lesion in the tail of the pancreas for more than 1 month.” On July 11, 2022, the patient was found to have pancreatic space-occupying lesions during physical examination. CT showed a suspicious low-density nodule in the body of the pancreas, and MRI scanning was recommended (Figure 1). The hepatic and renal function, routine blood, and serum tumor marker test results were normal. Also, the patient reported no apparent discomfort. Then, according to our recommendation, the patient underwent an MRI examination on July 26, 2022. It was indicated that the lesion with the rich blood supply in the tail of the pancreas should be examined by positron emission tomography (PET)-CT (Figure 2). Since the patient’s pancreatic space-occupying lesions could not be diagnosed as benign or malignant, it was recommended that the patient undergo a fluorodeoxyglucose (FDG) PET-CT examination. In order to further confirm the diagnosis, the patient underwent PET-CT examination on August 4, 2022. FDG PET-CT results revealed a slightly low-density shadow lesion in the tail of the pancreas and no central metabolism, and benign or low-grade malignant lesions were considered (Figure 3A). Ga-68 dotatate PET-CT results demonstrated that the space-occupying lesions in the pancreatic tail were likely PNETs (Figure 3B).

Considering that endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is the most effective test for diagnosing IPAS, we consulted the Radiology Department and expected to perform EUS-FNA on August 17, 2022. However, after consultation with the Radiology Department, they considered that the lesion was located in the body and tail of the pancreas, and there were many nearby splenic vessels, which limited the angle of EUS-FNA needle entry. Also, the pancreatic tail tissue was thin and prone to puncture-side injury. Considering the above factors, the Radiology Department did not perform EUS-FNA on this patient.

Combined with the previous examination results, the patient’s serum tumor markers were typical. The imaging examination demonstrated a space-occupying lesion in the tail of the pancreas, likely benign or of low-grade malignancy. Nonetheless, regarding the poor prognosis of pancreatic tumors, after we explained the surgical risks and condition in detail to the patient, the patient underwent robotic tail pancreatic tumor re-section on August 23, 2022. During the surgery, EUS detected a hypoechoic nodule in the tail of the pancreas, with a clear border and no clear blood flow signal on color Doppler flow imaging (Figure 4). The operation went smoothly, and the tumor was removed entirely from the tail of the pancreas. After the tumor’s complete resection at the pancreas tail, a round mass in the pancreas resembling spleen tissue was seen (Figure 5). Postoperative histopathology results showed that the group of the pancreatic tail was ectopic spleen tissue, the size was 1.3×1.0×0.8 cm, and the surrounding pancreatic lobules were clear (Figure 6). The patient recovered with no other complications and was discharged 5 days later.

Discussion

From our experience, IPAS should be considered in patients with hypervascular masses located in the tail of the pancreas. Patients often do not have any clinical symptoms, tumor markers are not elevated, imaging tests cannot distinguish IPAS from PNTs, and PET-CT has the potential for false-positive results. EUS-FNA is a necessary preoperative test for diagnosing IPAS through either cytology or histopathology.

Although previous studies have indicated that imaging data is an essential basis for diagnosing IPAS [7,36,37], in our case, CT, MRI, PET-CT, and EUS were not good for the differential diagnosis of IPAS. The previous studies found that IPAS should be considered when a smooth, round, solid hypervascular mass appears in the tail of the pancreas on abdominal CT [11,38]. In the present case, MRI suggested that the patient had a hypervascular lesion in the tail of the pancreas, the same imaging findings previously reported, while subsequent Ga-68 dotatate PET-CT results suggested a more likely neuroendocrine tumor of the pancreas. Lancellotti et al reported similar cases of pre-operative diagnosis of IPAS as PNET due to false-positive 68-Ga-Dotatoc PET-CT [39]. The density and signal intensity of the accessory spleen in the pancreas can be affected by pathological changes in the spleen, such as hemosiderosis and hypersplenism in leukemia and lymphoma [40]. This was also the main reason why imaging, including PET-CT, did not accurately diagnose IPAS. In this case, the patient was a 64-year-old man. The pancreatic mass did not show imaging signatures of hemorrhagic degeneration and heterogeneous enhancement, so the diagnosis of SPN was not prioritized.

Manoop et al [41] recommended that dynamic real-time EUS imaging could observe lesions connecting to the spleen through a bridge of spleen tissue, which could be used to distinguish IPAS from PNETs. We did not observe a similar phenomenon using EUS intraoperatively. The results of Grace et al [42] also proved that the diagnosis of IPAS by EUS criteria alone is inaccurate. EUS-FNA is still a reliable method for diagnosing IPAS [32–35]. For the present case, EUS-FNA may have been a better choice before surgery. However, surgical treatment was chosen at that time, considering the risk of puncture and the results of Ga-68 dotatate PET-CT. EUS-FNA carries the risk of infection [43], pancreatitis, and bleeding for pancreatic space-occupying lesions [44,45]. EUS-FNA can also cause seeding and metastasis of the tumor needle tract for tumor lesions [46]. Besides that, multivariate analysis confirmed the lower diagnostic accuracy of EUS-FNA for minor pancreatic lesions, especially those smaller than 5 mm [47]. In clinical diagnosis, it is necessary to combine imaging examinations of pancreatic masses to make a comprehensive judgment.

In the present case, the patient’s carbohydrate antigen (CA) 19-9 level was not abnormal. Although previous reports implied that IPAS might increase CA19-9 levels [48,49], this was not specific. Even though CA19-9 is a biomarker currently used to monitor pancreatic tumors, the phase-positive predictive value is only 72.3% [50]. This means that using CA19-9 to diagnose pancreatic tumors is not effective. From previous reports of IPAS, CA19-9 was found to be normal in the vast majority of patients. Nevertheless, various new methods can improve the diagnosis of IPAS, such as technetium-99m heat-damaged red blood cells (Tc-99m HDRBC) [51,52]. Using Tc-99m-labeled autologous HDRBCs, spleen tissue captured up to 90% of injected Tc-99m HDRBCs, whereas pancreatic neuroendocrine tumors did not [23]. Yet, there may be a correlation between the size of Tc-99m HDRBC and IPAS, and false negatives may occur when IPAS is less than 2 cm or when the spleen has minimal function [11].

Conclusions

This report has highlighted the importance of considering the diagnosis of IPAS in hypervascular lesions seen on imaging alone and of confirming the diagnosis with definitive cytopathological or histopathological examination.